RESEARC H Open Access Highly malignant soft tissue sarcoma of the extremity with a delayed diagnosis Jong Hoon Park 1* , Chang Ho Kang 2 , Chul Hwan Kim 3 , In Jung Chae 1 , Ji Hun Park 1 Abstract Purpose: To evaluate the characteristics of highly malignant soft tissue sarcoma of the extremity with a delayed diagnosis. Materials and methods: The clinical and radiological characteristics of 18 cases of highly malignant soft tissue sarcomas of the extremity with a delayed diagnosis were determined. Results: Ten men and eight women of mean age 44.8 years (range, 15-79 years) were included in this study. Seven cases of synovial sarcoma, three cases each of alveolar soft part sarcoma and malignant fibrous histiocytoma, two cases each of highly malignant leiomyosarcoma and myxofibrosarcoma, and one case of clear cell sarcoma were enrolled. Times from tumor detection to diagnosis ranged from 1 to 3 years in most cases; three of the seven synovial sarcoma cases took more than 10 years to diagnose. Of the seven cases of synovial sarcoma, five cases of small, superficial located masses were simply excised without a pre-surgical biopsy. Three cases of alveolar soft part sarcoma showed characteristic T1- and T2-weighted high signal intensities with signal voids in MR images. In addition, one synovial sarcoma patient and one alveolar soft part sarcoma patient showed evidence of calcification on plain radiographs. However, no general characteristic clinical findings were found to be common to the 18 cases. Conclusions: Contrary to general expectations, some soft tissue tumors that grow slowly are painless, and those that occur in superficial limbs may be highly malignant. Thus, even when a slow growing, painless superficial mass is encountered in a limb, physicians should keep the possibility of highly malignant soft tissue sarcoma in mind. Introduction Soft tissue sarcomas that develop in the limbs and the axial area, even those that are diagnosed early using appropriate methods and are treated adequately, have a 5-year survival rate of between 62 and 84% [1,2]. Early diagnosis is extremely important for the successful treat- ment of soft tissue sarcoma. However, delayed diagnosis of soft tissue sarcoma is common. The reasons for these delays are variable, and include, slow-growth, no pain, no palpation due to a deep-s eated location, and doctor- associated and socioeconomic factors. Because a sub- stantial proportio n of soft tissue sarcomas can grow for a long time without pain, they are often misdiagnosed due to the belief held by a large number of clinicians and the general populations that malignant tumors are painful, grow rapidly, and adhere strongly to adjacent tissues, and thus, slow growing, highly malignant soft tissue sarcomas may not be diagnosed, which is likely to result in poor outco mes and become the basis of dis- putes between physicians and the patient’s relatives. Furthermore, because tumor growth rates are subjective, no definition of a slow growing tumor exists in the lit- erature. According to a study by Lawrence et al. [3], approximately 60% of patients with a soft tissue sarcoma knew they had a tumor, and these patients were diag- nosed within 6 months of this realization. In this study, we defined a slow-growing tumor as one that patients had been aware of for over a year, and using this criter- ion, we analyzed highly malignant, slowly growing soft tissue sarcoma cases clinically and radiologically. Here, we describe the characteristics of these tumors and pro- vide a review of the literature. Materials and methods Of 31 cases with a diagnosis of highly malignant (Grade III according to the WHO classification) soft tissue sarcoma * Correspondence: pjh19642001@yahoo.co.kr 1 Department of Orthopedic Surgery, College of medicine, Korea University, Anam Hospital, Seoul, Korea Full list of author information is available at the end of the article Park et al. World Journal of Surgical Oncology 2010, 8:84 http://www.wjso.com/content/8/1/84 WORLD JOURNAL OF SURGICAL ONCOLOGY © 2010 Park et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative C ommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduct ion in any medium, provided the original work is properly cited. of the limb treated at our hospital between July 1997 and December 2008, we analyzed 18 cases in which the delay between patient awareness of the tumor and diagnosis exceeded 1 year. Highly malignant soft tissue sarcoma was diagnosed based on entries in final pathology reports. The male to female ratio of our cohort was 10:8, and mean patient age was 44.8 years (range 15 to 79 years). The characteristics of the 18 cases of highly malignant soft tissue sarcoma were ana- lyzed based on tumor types determined at final diagno- sis, times from patient recognition to diagnosis, the anatomical locations of tumors in limbs, depths of tumor locations in tissue (dichotomized as deep or superficial), tumor sizes, and the characteristics of tumors as determined by plain radiography and MRI. Results Seven cases of synovial sarcoma, three cases each of alveolar soft part sarcoma and malignant fibrous histiocytoma, two cases each of myxofibrosarcoma and high-grade leiomyosarcoma, and one case of clear cell sarcoma were diagnosed. Four of the seven cases of syno- vial sarcoma, two of the three cases of alveolar soft part sarcoma, two cases of myxofibrosarcoma, and one case each of high-grade leiomyosarcoma and clear cell sarcoma were transfer red to our hospital after surger y or biopsy at another hospital. For the remaining 8 cases, all procedures from biopsy to final surgery were performed at our hospital. Affec ted areas included the thigh (four cases), the lower leg ( six cases), the foot and ankle joint (three cases), the forearm (four cases), and the popliteal area (one case). Pulmonary metastasis was detected at diagnosis in all alveolar soft part sarcoma cases and in one clear cell sarcoma case. However, no distant metasta- sis was detected in the other tumor cases. In six cases, primary tumors were located in a deep region, and in twelve cases, they were located superficially. All three malignant fibrous histiocytoma cases occurred in patients in their 70 s, whereas the alveolar soft part sarcomas occurred in one child (>10 years old), and in one 20 and one 30 year old. Synovial sarcomas occurred in indivi- duals with ages at onset ranging from the second to the sixth decade, but it occurred preferentially in adults. Delays between tumor recognition by a patient to diagno- sis were between 1 and 3 years in most cases. However, in three cases of synovial sarcoma, it took more than 10 years to reach a diagnosis, and in another case of synovial sarcoma, it took more than 5 years. In one case of synovial sarcoma, recurrence occurred at the primary tumor location several times over 20 years. No common characteristic findings were evident by plain radiography, although one case of synovial sarcoma (Figu re 1) and one case of alveolar soft part sarcoma showed calcification on plain radiographs. In all three cases of alveolar soft part sarcoma, the characteristic MRI finding was of high sig nal intensity with signal voiding on T1 and T2 images (Figu re 2), which was attributed to the presence of abun- dant blood vessels. However, no other tumor-specific findings were evident. A diagnostic biopsy was only performed in one of the seven synovial sarcoma cases. In this case, a relatively large tumor was fixed in the superficial layer prior to final operation. However, in t he other six cases, simple excision was performed without a pre-surgical biopsy because tumors were small or superfi- cially located. In contrast to synovial sarcoma cases, diag- nostic biopsies were performed in all malignant fibrous histiocytoma and alveolar soft part sarcoma cases due to a relatively large tumor size or a deep location. Discussion Some types of soft tissue sarcoma that develo p in the limbs or axial skeleton grow slowly over several years, or remain the same size for years or even decades, and then suddenly start to g row. Because these tumors are painless and movable by palpation in many cases, they are often misdiagnosed as benign tumors, and simple excision is performed without adequate pre-surgical eva- luation. Importantly, if simple excision is performed without b iopsy, the tumor can rec ur several years later, when all concerned will be taken aback by its aggressive nature. Both physic ians and patients have a precon- ceived idea that malignant tumors are painful and grow rapidly. Furthermore, soft tissue sarcomas are much rarer than benign tumors, and thus, physicians often fail to recommend ap propriate tests or perform a compre- hensive biopsy. In addition, patients may not even Figure 1 A plain radiograph showing a well-defined soft tissue mass with marginal calcification posterior to the distal femur. There is no evidence of associated bone erosion in this patient. This is an example of a synovial sarcoma in one of its more common locations. Park et al. World Journal of Surgical Oncology 2010, 8:84 http://www.wjso.com/content/8/1/84 Page 2 of 5 consider consulting a physician in some cases because they do not consider the tumor to be serious. Tumors thatdonotchangeorchangeonlyslowlyovertimeare often considered benign, but tumor growth rate should notformthebasisofadiagnosis.AccordingtoLawr- ence et al. [3], approximately 50% of soft tissue sarcoma patients are diagnosed at about 4 months after patient recognition, and an additional 20% are diagnosed after 6 m onths. Furthermore, because the literature provides no precise definition of ‘slowly-grow ing’ sarcoma, we considered a slow-growing tumor to be one known to the patient for more than one year pri or to diagnosis. Synovial sarcoma is a representative type of slowly growing highly malignant tumor, and it has been reported that in synovial sarcoma cases, a substantial proportion of patients have an average symptomatic per- iod of 2 to 4 years, though in some rare cases, this per- iod has been reported to be longer than 20 years [4]. Of the 18 subjects enrolled in the present study, one case had a symptomatic period of 20 years, and four of the seven synovial sarcoma cases had a symptomatic period of 5-6 years (Table 1). For the reasons listed above, the diagnosis of synovial sarcoma is frequently delayed. In some previous studies, ~20-30% of patients have presented with calcificationonplainradiographs [5-7]. Similarly, in our study, calcific density was observed by plain radiograp hy in one case with a tumor in the popliteal area. Sixty percent of soft tissue sarcoma cases occur in the limbs, and the most prevalent affected region is the distal f emoral area around the knee joint [8]. Consistent with previous studies, we found that these tumors occurred in individuals with diverse ages ranging from adolescents to adults. To determine the disease stage of soft tissue sarcoma, tumor growth rate and size, and location within tissue should be consid- ered. Characteristics worth noting are that most highly malignant sarcomas are located deep within limb mus- cles, and that tumor sizes are larger than 5 cm [9]. In the present study, six of seven synovial sarcoma cases were located in superficial areas, but these were small tumors with a long axis of less than 5 cm in four cases. For these reasons, six of the seven were excised without sufficient biopsy or examination. The characteristics of the alveolar soft portions of sarcomas are that they com- prise only 0.5-1.0% of soft tissue sarco mas, grow slowly, have metastasized in 20-25% of cases at diagnosis, respond poorly to chemotherapy, and have a poor prog- nosis [10,11]. Onse t usually oc curs during adolescenc e or in young a dults, and the only symptom is restriction of joint movement. In our study, one of the three cases of alveolar soft part sarcoma occurred in adolescence, and the other two occurred in young adults. In two of these three cases, the chief complaint was of a painless tumor, whereas the third admitted restricted joint move- ment with mild pain. At time of diagnosis, pulmonary metastasis was detected in all three cases. In contras t to other soft tissue sarcomas, alveolar soft part sarcomas have characteristic radiologic features, that is, MRI T1- and T2-weighted images have high signal intensities and signal voids due to the presence of abundant blood ves- sels [12-14]. Accordingly, these tumors can be misdiag- nosed as hemangiomas or A-V malformations. In the present study, one case was attributed to hemangioma at initial examination. In alveolar soft part sarcom as, solid tumor tissues are surrounded by vascular tissues and blood flow wash-out is slow. In contrast, A-V malformations are comprised of pure vascular tissue without accomp anying tissues, and blood flow wash-out Figure 2 MRI images of an alveolar soft part sarcoma. (A) An axial T1-weighted fat-suppressed image and (B) an axial T2-weighte d image. High signal on T1FS, T2WI with multiple signal voids are apparent. Park et al. World Journal of Surgical Oncology 2010, 8:84 http://www.wjso.com/content/8/1/84 Page 3 of 5 is rapid, which enables the differentiation of these two conditions [14-16]. Since most soft tissue sarcomas lack defined radiologi- cal characteristics, it is not easy to differentiate sarco- mas, even by MRI. Nonetheless, alveolar soft part sarcomas do have specific imaging results, and thus, imaging tests may play a decisive diagnostic role. The general characteristics of most sarcoma s are that they grow quickly, are located deep within tissue, and are relatively large. As shown by the present study, the char- acteristics of some types of soft tissue sarcomas contrast with the traditionally held opinion that they are small slow-growing masses with a superficial location. Fortu- nately, non-speci fic soft tissue sarcomas are uncommon, and if preconceived notions are avoided, they can be diagnosed early. Synovial sarcoma cases occur primarily in adults in the vicinity of the knee joint and in the lower leg, and the tumors grow slowly and o ccur super- ficially. On the other hand, alveolar soft part sarcomas occur in adolescents and young adults, and are found preferentially around the knee joint and have specific MRI characteristics. Conclusions According to this study, some soft tissue tumors that grow slowly are painless, and some that occur in the superficial limbs may be highly malignant. The most important characteristic of soft tissue sarcomas is their non-specific nature. Thus, even when a slow growing, painless superficial mass i s encountered in the limbs, after eliminating absolutely benign possibilities, such as, a ganglion of the wrist or lipoma of the back, physicians must consider the possibility of sarcoma and conduct a careful examination. Author details 1 Department of Orthopedic Surgery, College of medicine, Korea University, Anam Hospital, Seoul, Korea. 2 Department of Radiology, College o f medicine, Korea University, Anam Hospital, Seoul, Korea. 3 Department of Pathology, College of medicine, Korea University, Anam Hospital, Seoul, Korea. Authors’ contributions JoHP drafted the manuscript, ChaHK and ChuHK participated in the design of the study, IJC and JiHP conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 27 June 2010 Accepted: 23 September 2010 Published: 23 September 2010 References 1. Noria A, Davis A, Kandlel R, Levesque J, O’Sullivan B, Wunder J, Bell R: Residual disease following unplanned excision of soft tissue sarcoma of an extremity. J Bone Joint Surg 1996, 78A:650-5. 2. Simon MA, Enneking WF: The management of soft-tissue sarcomas of the extremities. J Bone Joint Surg 1976, 58A:317-27. 3. Lawrence W Jr, Donegan WL, Natarajan N, Mettlin C, Beart R, Winchester D: Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons. Ann Surg 1987, 205(4):349-59. 4. Enzinger FA, Weiss SW: Soft tissue tumors. St. Louis, Missouri, 3 1995, 757-86. 5. Menendez LR, Brien E, Brien WW: Synovial sarcoma, A clinicopathologic study. Orthop Rev 1992, 21:465-71. Table 1 Clinical data of all materials No Gender Age (Yrs) Duration (Yrs) Diagnosis Pain Location Depth Size Previous biopsy 1 M 42 6 S S No thigh deep 12 × 7 × 7 N 2 M 27 20 S S No forearm superficial 3 × 2 × 2 N 3 F 53 2 S S mild ankle superficial 1.8 × 1.2 × 0.5 N 4 F 53 10 S S mild foot superficial 5 × 5 × 6 Y 5 M 15 1 S S No ankle superficial 3 × 3 N 6 F 28 1 S S mild forearm superficial 2 × 2 N 7 M 40 10 S S Yes popliteal superficial 5 × 5 N 8 M 70 1 MFH No thigh superficial 9 × 4 Y 9 F 79 3 MFH No forearm superficial 15 × 7 Y 10 M 69 1 MFH No lower leg superficial 5 × 2 Y 11 F 16 1 Alv SS mild thigh deep 5 × 4 × 3 Y 12 M 27 3 Alv SS yes lower leg deep 7 × 4 × 11 Y 13 M 32 3 Alv SS yes lower leg deep 15 × 7 × 6 Y 14 M 72 3 HGL No thigh deep 4 × 4 × 5 Y 15 F 68 3 HGL No lower leg superficial 5 × 4 × 3 N 16 F 52 2 MFS mild lower leg superficial 14 × 9 Y 17 M 31 1 MFS mild lower leg deep 10 × 5 Y 18 F 50 1 CS No forearm superficial 2 × 3 N M: male, F: female, S S: synovial sarcoma, MFH: malignant fibrous histiocytoma, HGL: high grade leiomyosarcoma, Alv SS: alveolar soft part sarcoma, CS: clear cell sarcoma, MFS: myxofibrosarcoma. 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Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Park et al. World Journal of Surgical Oncology 2010, 8:84 http://www.wjso.com/content/8/1/84 Page 5 of 5 . Seven cases of synovial sarcoma, three cases each of alveolar soft part sarcoma and malignant fibrous histiocytoma, two cases each of highly malignant leiomyosarcoma and myxofibrosarcoma, and one case. leiomyosarcoma, and one case of clear cell sarcoma were diagnosed. Four of the seven cases of syno- vial sarcoma, two of the three cases of alveolar soft part sarcoma, two cases of myxofibrosarcoma,. evaluate the characteristics of highly malignant soft tissue sarcoma of the extremity with a delayed diagnosis. Materials and methods: The clinical and radiological characteristics of 18 cases